Isolated and Syndromic Retinal Dystrophy Caused by Biallelic Mutations in RCBTB1, a Gene Implicated in Ubiquitination.

Inherited retinal dystrophies (iRDs) are a group of genetically and clinically heterogeneous conditions resulting from mutations in over 250 genes. Here, homozygosity mapping and whole-exome sequencing (WES) in a consanguineous family revealed a homozygous missense mutation, c.973C>T (p.His325Tyr), in RCBTB1. In affected individuals, it was found to segregate with retinitis pigmentosa (RP), goiter, primary ovarian insufficiency, and mild intellectual disability. Subsequent analysis of WES data in different cohorts uncovered four additional homozygous missense mutations in five unrelated families in whom iRD segregates with or without syndromic features. Ocular phenotypes ranged from typical RP starting in the second decade to chorioretinal dystrophy with a later age of onset. The five missense mutations affect highly conserved residues either in the sixth repeat of the RCC1 domain or in the BTB1 domain. A founder haplotype was identified for mutation c.919G>A (p.Val307Met), occurring in two families of Mediterranean origin. We showed ubiquitous mRNA expression of RCBTB1 and demonstrated predominant RCBTB1 localization in human inner retina. RCBTB1 was very recently shown to be involved in ubiquitination, more specifically as a CUL3 substrate adaptor. Therefore, the effect on different components of the CUL3 and NFE2L2 (NRF2) pathway was assessed in affected individuals' lymphocytes, revealing decreased mRNA expression of NFE2L2 and several NFE2L2 target genes. In conclusion, our study puts forward mutations in RCBTB1 as a cause of autosomal-recessive non-syndromic and syndromic iRD. Finally, our data support a role for impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations

Pion photoproduction on the nucleon in the quark model

We present a detailed quark-model study of pion photoproduction within the effective Lagrangian approach. Cross sections and single-polarization observables are investigated for the four charge channels, $\gamma p\to \pi^+ n$, $\gamma n\to \pi^- p$, $\gamma p\to \pi^0 p$, and $\gamma n\to \pi^0 n$. Leaving the $\pi N\Delta$ coupling strength to be a free parameter, we obtain a reasonably consistent description of these four channels from threshold to the first resonance region. Within this effective Lagrangian approach, strongly constrainted by the quark model, we consider the issue of double-counting which may occur if additional {\it t}-channel contributions are included.Comment: Revtex, 35 pages, 16 eps figures; version to appear on PR

Photoproduction of pions and properties of baryon resonances from a Bonn-Gatchina partial wave analysis

Masses, widths and photocouplings of baryon resonances are determined in a coupled-channel partial wave analysis of a large variety of data. The Bonn-Gatchina partial wave formalism is extended to include a decomposition of t- and u-exchange amplitudes into individual partial waves. The multipole transition amplitudes for $\gamma p\to p\pi^0$ and $\gamma p\to n\pi^+$ are given and compared to results from other analyses.Comment: 18 pages, 14 figure

P-wave excited baryons from pion- and photo-induced hyperon production

We report evidence for $N(1710)P_{11}$, $N(1875)P_{11}$, $N(1900)P_{13}$, $\Delta(1600)P_{33}$, $\Delta(1910)P_{31}$, and $\Delta(1920)P_{33}$, and find indications that $N(1900)P_{13}$ might have a companion state at 1970\,MeV. The controversial $\Delta(1750)P_{31}$ is not seen. The evidence is derived from a study of data on pion- and photo-induced hyperon production, but other data are included as well. Most of the resonances reported here were found in the Karlsruhe-Helsinki (KH84) and the Carnegie-Mellon (CM) analyses but were challenged recently by the Data Analysis Center at GWU. Our analysis is constrained by the energy independent $\pi N$ scattering amplitudes from either KH84 or GWU. The two $\pi N$ amplitudes from KH84 or GWU, respectively, lead to slightly different $\pi N$ branching ratios of contributing resonances but the debated resonances are required in both series of fits.Comment: 22 pages, 28 figures. Some additional sets of data are adde

Properties of baryon resonances from a multichannel partial wave analysis

Properties of nucleon and $\Delta$ resonances are derived from a multichannel partial wave analysis. The statistical significance of pion and photo-induced inelastic reactions off protons are studied in a multichannel partial-wave analysis.Comment: 12 pages, 8 Table